It is a malignant tumour that originates in the prostate gland. Cancer occurs when a group of cells begins to multiply out of control and invades surrounding tissues; it may also spread to distant tissues or organs through lymphatic or vascular circulation, which is known as metastasis. The prostate contains various cell types, but the majority (95%) of prostate cancers originate in glandular cells that produce secretions during ejaculation. This type of cancer is called adenocarcinoma of the prostate.

Prostate with sites of carcinoma

Autopsy studies have revealed the presence of prostate cancer in one out of every three examined males, but 80% of these tumours are very small in size and are clinically insignificant. Autopsies in 70-year-old patients show that 46% of males have prostate cancer, but fortunately, it is very slow growing compared to other cancers. About 90% of prostate cancers remain latent over decades. Microscopic foci of adenocarcinoma can be found in 85-90% of men over 80 years of age, which confirms that most men with prostate cancer die from causes unrelated to the malignant tumour.In Spain, prostate cancer is the 3rd leading cause of death due to cancer after lung and colon cancers. The incidence and mortality of this cancer in our country is one of the lowest in Europe, along with Italy and Greece. It is estimated that one out of six men will develop prostate cancer over his lifetime, and nine out of ten cases appear after 65 years of age.

Are there risk factors for developing prostate cancer?Although the specific factors responsible for the origin and progression of prostate cancer are still unknown, it is known that certain genetic and environmental factors are associated with the emergence and development of the disease.

Genetic and familial factorsMen who have first degree family members (father or brothers) affected by prostate cancer, especially if diagnosed before 55 years of age, are at higher risk of developing from the disease. About 15% of prostate cancers are hereditary. A specific gene, HPC1, is associated with a high likelihood of having the disease.

AgeAge is the most important risk factor, since the probability of having prostate cancer increases with age: it is rare below 40 years of age, and begins to occur at 50. Two out of three prostate cancer cases occur in men greater than 65 years of age.

Race and geographyIn African-American men, prostate cancer is more frequent, more aggressive, and appears at an earlier age. In Europe, the incidence is greater in Scandinavian countries, and the frequency diminishes as one travels further south, leading to the hypothesis that incidence may be associated with varying exposure to sunlight. It is less frequent in Africa, Asia, and Latin America; although it is believed to be due more to dietary factors than ethnic factors, since Asians living in the United States have a greater incidence of prostate cancer than those living in Asia.

HormonesMale sexual hormones (androgens) are essential to the development and growth of the prostate and play an important role in carcinogenesis of the prostate. High levels of other hormones such as insulin growth factor type 1 (IGF-1) are associated with prostate cancer.

Inflammation and infectionChronic inflammatory processes that produce an increase in cellular replication to replace damaged tissue contribute to the development of cancers such as those of the oesophagus, stomach, liver and bladder. Some studies suggest that prostate cancer may have an infectious cause (papillomavirus, herpesvirus or cytomegalovirus) in the setting of genetic or acquired deficiency in cellular defence mechanisms against the infection.

ObesityObesity is clearly associated colon and breast cancers. By reducing the consumption of fats and increasing physical exercise, oxidative stress can be reduced, thereby possibly lowering the risk of prostate cancer.

DietIt has been shown that dietary factors are important in colon and breast cancers. In 1998 it was observed that prostate cancer mortality was inversely related to consumption of cereals, nuts, olive oil and fish.

FatsThe incidence and mortality of prostate cancer is closely related with the consumption of polyunsaturated fats, red meats, dairy and eggs. In animal studies, high levels of fat stimulate proliferation of prostate cancer cells, and a fat-free diet can reduce the growth of the tumours. Another factor that may explain the association of diets rich in fats and prostate cancer is that diets rich in red meats usually also include little vegetable ingestion. In addition, diets rich in dairy, meat and eggs are also rich in calcium and zinc, two substances that may increase the risk of prostate cancer.

SoyLegumes constitute a very important energy source in Asian diets, where the incidence of prostate cancer is low. As has been shown in research animals, soy beans are rich in isoflavones (genistein and daidzein), two substances with weak estrogenic activity that are capable of inhibiting the growth of both benign and malignant prostatic cells, and reducing the growth of tumours.

LycopeneLycopene is a pigment found in tomatoes and other red fruits. It is a beta-carotene with potent antioxidant activity that in laboratory in vitro studies has been shown to inhibit the growth of benign and malignant prostatic cells. However, currently there are no scientific studies clearly demonstrating the beneficial effects of lycopene consumption in prostate cancer cases.

Green teaWidely consumed in Asia, where the incidence of prostate cancer is low, green tea contains antioxidant substances called polyphenols. In vitro and animal studies have shown that epigallocatechin, the principal polyphenol in the green tea leaf, inhibits growth of tumour cells.

FishA recent study has shown that high consumption of fish, if not associated with incidence of prostate cancer, does decrease risk of death by up to 63% in patients already diagnosed with the disease, probably due to anti-inflammatory effects of fish oils that may halt the growth of a malignant tumour.

Alcohol consumptionThe consumption of one to three glasses of wine has a protective effect, presumably due to high content of polyphenols with antioxidant activity.

TobaccoTobacco is not a direct cause of higher incidence of prostate cancer, although it has been shown to be associated with both a more advanced state of disease at the time of diagnosis and with higher mortality.

Do vitamin and mineral supplements prevent prostate cancer?No. In the SELECT study involving more than 35,000 men followed over seven years, vitamin E and selenium supplements had no effect on risk of prostate cancer. In another study, PSHS II, no effect was shown using either vitamin C or vitamin E. Current scientific evidence suggests that neither selenium nor vitamins E or C should be used for the prevention of prostate cancer.

What symptoms does prostate cancer cause?In initial stages, while the tumour is confined to the prostate, there are no symptoms since most tumours are distant from the urethra. In advanced stages symptoms may occur due to urinary obstruction, such as those seen in obstructive BPH: hematuria (blood in the urine), impotence, urinary incontinence. When the disease has spread to other sites, there may also be bone pain in the back, ribs, and other bones.

How is prostate cancer diagnosed?Currently the two basic or first-line tools that allow detection of prostate cancer are PSA (prostate-specific antigen) values and rectal examination. A combination of both of these is the most useful method of determining a patient’s risk of prostate cancer.

What is PSA?The PSA (prostate-specific antigen) is a substance (more specifically, a protein) that is secreted by prostatic cells and is found in high concentrations (mg/ml) in semen. Its function is to liquefy the semen. A small quantity of PSA (ng/ml) is present in the blood in two forms: total PSA and free PSA. The levels of PSA in blood may be altered by age, the presence of diseases affecting the prostate (BPH, prostate cancer and prostatitis) or by performing urethral manipulations or surgical interventions on the prostate. In these cases PSA escapes from prostatic cells and enters the blood, which may be detected during analysis. The relationship between total PSA and free PSA is an important factor in determining if there is benign hyperplasia of the prostate (BPH) when the values are above 20%. Severely obese men tend to have lower values of PSA. There are certain drugs, such as finasteride or dutasteride, and some herbal preparations, that lower PSA levels. In these cases, a correction factor must be applied to determine an accurate level of PSA.

What are normal PSA values?In men under 50, a normal PSA should be under 2.5 ng/ml; between 50-59 years, below 3.5 ng/ml; between 60-69, below 4.5 ng/ml; and between 70 and 79 years, below 6.5 ng/ml. Other factors, such as the size of the prostate, the presence of BPH, the annual increment of PSA, the association between PSA and prostatic volume, or the association between total PSA and free PSA, contribute to improving the sensitivity (ability to detect more cancers) and specificity (avoiding unnecessary biopsies) of the tests, helping to better differentiate patients whose high levels of PSA are due to prostate carcinoma.

What is the probability of having prostate cancer if PSA levels are elevated?For a 50-year-old male, a normal rectal exam and PSA values between 0.0-2.0 ng/ml, the probability of having prostate cancer is 10%. If PSA is 2.0-4.0 ng/ml, the probability is 15-25%. If the PSA is 4.0-10.0 ng/ml, the probability is 17-32%, and with PSA levels above 10.0 ng/ml, the probability is 43-65%.

Are there other tumour markers to detect prostate cancer?Yes, PCA3 is a new tumour marker to diagnose prostate cancer. This test detects the presence of messenger RNA expressed by gene 3 of cancer cells, with very elevated concentrations found in prostatic fluid in almost all cases of carcinoma. The test is performed on a urine sample collected after a rectal exam. The result is considered positive for values above 35 and has a sensitivity of 68% and a specificity of 78%. It is a useful marker for deciding whether to perform biopsies in patients with elevated PSA values and previously negative biopsies.

Should all men undergo prostate cancer screening?No, screening is not necessary in asymptomatic men and those with life-expectancy under 10 years. At 75 years of age only 50% of men have a life-expectancy greater than 10 years, therefore after this age screening is not recommended. On the other hand due to the disparity between high prostate cancer prevalence and low mortality risk, distinguishing between aggressive tumours and clinically insignificant ones is very important.

At what age should prostate cancer screening begin?In men with family history of prostate cancer in a father or brother (diagnosed before age 65) or of African-American race, an annual PSA test is recommended beginning at age 40. In very high risk men (several family members diagnosed before age 65) it is recommended starting at age 35. In men without risk factors screening may be started at age 45. In general, it is not necessary in men over age 75, neither is it recommended in patients with a life-expectancy less than 10 years.

What is a digital rectal exam?It is an exam performed by a physician by introducing a gloved and lubricated finger into the anal canal to be able to detect deformities in the contour or irregularities in the consistency of the prostate. Although it is less effective than the PSA to detect prostate cancer, it aids in detecting a malignant tumour in men whose PSA levels are normal.

Digital rectal exam

Prostate biopsyThe biopsy involves obtaining samples of prostate tissue that are then examined under a microscope by a pathologist to determine the existence of cancerous cells. Normally, an urologist performs the procedure. The samples are obtained with the aid of images from an ultrasound probe placed in the rectum. Next, an 18-20 gauge needle is inserted through the rectum or perineum and 1cm long, 1mm wide cores are taken from different regions of the prostate, and if necessary, the seminal vesicles. The transrectal route is used to obtain an average of 21 cores (between 10 and 40), and the transperineal route when more than 40 cores are desired.The number of cores obtained, as well as the percentage and grade of tumour in each of the cores, are important, since they help to determine the probability of an aggressive tumour.

Schemes of a prostate biopsy

Is the prostate biopsy painful?It should not be painful. For over 15 years, biopsies have been performed under IV sedation in cooperation with an anaesthetist, similar to IV sedation used for GI endoscopy procedures. The procedure lasts 10-20 and the patient may be discharged in a few hours.

What are the possible complications of a prostate biopsy?The most serious complication is an infection of the prostate (acute bacterial prostatitis) that, if severe, could lead to sepsis. Although this complication is infrequent (0.5-3.5%), our centre uses local antiseptic techniques that reduce the possibility of infectious complications to less than 0.01%. After the biopsy, the presence of small amounts of blood in semen is very common, that may last for several weeks, or blood in the urine (dark urine) that may be present for several days.

Biopsy results: tumour gradeThe pathologist provides a report assigning a score to the malignant tumour cells. This scoring system is called the Gleason grade, from 1-5, with grade 5 being the most aggressive. A sum of two grades is established: the primary score is that of the most predominantly found, and the secondary score is the next most predominant one. The sum of the two determines the Gleason score, from 2 to 10.Tumours with Gleason scores of 2 to 4 are very rare and have very low aggressive potential, Gleason scores between 5 and 6 are intermediately aggressive, and scores above 7 are highly aggressive.

Is PSA an important predictor of response to treatment?Yes, since PSA values indicate the risk that the disease has spread beyond the prostate, invading the seminal vesicles and lymphatic glands. Patients with PSA values under 10 ng/ml at the time of diagnosis are more likely to respond to radical treatment.

I have been diagnosed with prostate cancer. What phase or stage am I in?Staging shows the size and spread of the tumour. This data is very important because tumours localized to the prostate respond better to treatment. The TNM system (Tumour, lymphatic Nodes, and Metastasis) is the system used currently. Localized cancer is classified as T1a when rectal exam is normal. A value of T2a indicates that rectal exam is abnormal but there are no signs of spread beyond the prostate. A value of N0 indicates there is no spread to regional lymphatic glands. An M0 phase indicates there are no signs of metastasis. If the cancer has spread to lymphatic glands it is classified as N1, and if it affects the bones, as M1.

Risk groups in patients diagnosed with prostate cancerAlgorithms have been developed based on PSA values, Gleason score and T staging (TNM system) in association with mortality due to prostate cancer after radical surgery or radiotherapy.

Low risk: PSA equal to or less than 10 ng/ml, Gleason score equal to or less than 6, and stage T1c or T2a.Intermediate risk: PSA between 10 and 20 ng/ml, Gleason score of 7, and stage T2b.High risk: PSA greater than 20 ng/ml, Gleason score between 8 and 10, and stage T2b or T3.

Are there other tests to determine if the cancer has spread?In general, in patients with low risk disease, it is not necessary to perform endorrectal computed tomography (CT) or MRI, which are necessary in patients in intermediate or high risk groups. A bone scan should be performed if there is suspicion of bone involvement, and/or in cases of PSA levels above 10 ng/ml. In some cases a PET scan is performed to evaluate for presence of metastasis.

Endorrectal magnetic resonanceThis is an imaging technique that uses magnetic waves instead of X rays. The energy in the magnetic waves is absorbed by the body, and then liberated, providing the most detailed images of the prostate that can currently be obtained. The quality of the images, sometimes associated with spectroscopy or injection of paramagnetic contrast, is so high as to allow observation of areas with BPH, and if a tumour is present, to differentiate between tumour stage T2 or T3 with a specificity of 95%. It also permits detection of enlarged pelvic lymph nodes, and is a great aid in planning biopsies by indicating areas suspected of harbouring cancer cells.

Bone scanThis is a test that allows us to detect if the tumour has invaded the bones. It involves injecting a radioactive isotope in the vein that fixes on areas where the bone is damaged. A special camera detects accumulations of radioactivity and forms an image of the whole skeleton. These accumulations also appear in cases of inflammatory processes (arthritis), old areas of trauma or other bone pathologies.

What are treatment options for localized prostate cancer?An alternative exists for patients in the low risk group of maintaining watchful waiting and not undergoing any treatment. The most effective treatments in initial phases of the disease are radical prostatectomy, external radiotherapy, and brachytherapy.

What is watchful waiting?The great disparity between high incidence of prostate cancer and the low mortality rate demonstrates that many men do not need definitive treatment for localized disease. It is therefore important to distinguish those tumours that are likely to progress, since these should be treated definitively, and reduce the risk of therapeutic procedures in those tumours likely not to progress.

Who are candidates for watchful waiting?Patients in the low-risk group are candidates for watchful waiting since they have a very low probability of the disease progressing in 10 to 15 years after diagnosis. Follow-up includes periodic PSA levels (2-3/year), rectal exam and/or repeat biopsies to determine if the tumour has changed in size or Gleason score. If the tumour progresses, further treatments should be discussed.

External radiotherapyExternal radiotherapy has been used for the treatment of prostate cancer since 1930. In the late 1960s, the first linear accelerators appeared that safely permitted increasing the amount of radiation. In 1980, computed tomography emerged, that allowed for greater precision and decreased toxicity to the bladder, rectum and small intestine. In the 1980s and 1990s the dose was able to be increased up to 75-79 Gy. Thanks to intensity-modulated radiation therapy (IMRT), implemented in the mid-1990s, placement of small intraprostatic markers achieved greater therapeutic response and a reduction in adverse effects. Treatment is painless and is carried out over 5-6 weeks.External radiotherapy is contraindicated in patients with inflammatory bowel disease (ulcerative colitis, Crohn’s disease) or who have had previous pelvic radiation treatment. In patients with a Gleason score equal to or greater than 7 or PSA levels greater than 10 ng/ml, radiotherapy is combined with hormone-blocking drug therapy (chemical castration). Patients with obstructive urinary symptoms are not good candidates for this treatment, since there is increased risk of urinary retention.

What adverse effects may I suffer due to external radiotherapy?

Intestinal problemsDuring and after treatment, patients may have diarrhoea, sometimes bloody, and anal incontinence, but usually both of these disorders disappear with time. About 5-10% of patients have irritable bowel syndrome and rectal bleeding.

Urinary problemsPatients may have increased urinary frequency, feel burning on urination and may observe blood in the urine. Over time symptoms improve, although 5-10% of patients continue to have urinary frequency and episodes of blood in the urine. However, urinary incontinence is seen much less commonly than after radical surgery.

Sexual problemsAfter a couple of years after completing treatment, the degree of erectile dysfunction is similar to that present in patients who underwent radical prostatectomy. In men with normal erections prior to radiotherapy, 50% present with severe erectile dysfunction 5 years after treatment. Treatment for the erectile dysfunction includes PDE-5 inhibitor medications (sildenafil, vardenafil, tadalafil), or vacuum devices or penile implants in cases refractory to treatment.

BrachytherapyBrachytherapy consists of placement of radioactive seeds within the prostate, whether permanently (LDR brachytherapy) or temporarily (HDR brachytherapy). Its use began in the 1920s with the placement of Ra (radium) seeds, which were later substituted by 125I (iodine isotope) in the 1960s, in both cases via small surgical interventions, but the procedure was abandoned due its low efficacy and serious complications. In the 1980s a technique was developed to implant seeds the size of a grain of rice (LDR brachytherapy) through the skin between the scrotum and anus (perineum), using transrectal ultrasound with 125I (iodine isotope) and 103Pd (palladium isotope). HDR brachytherapy uses 192Ir (iridium isotope) or 137Cs (cesium isotope), and the seeds are removed after treatment. The procedure is performed in an operating room under spinal anaesthesia. This technique is not recommended in patients with a prostate larger than 50-60 cc, and/or severe obstructive urinary symptoms, or in patients who have previously undergone TUR or prostatectomy due to BPH, since the placement of the seeds may be very complicated in these cases.

What adverse effects may occur after brachytherapy?

Intestinal problemsRectal complaints (proctitis) are much less common than in external radiotherapy, and if they do occur, disappear in little time.

Urinary problemsThese are more frequent than in the external radiotherapy group, mainly in patients presenting with BPH and obstructive urinary symptoms. After brachytherapy, up to 22% of patients have acute urinary retention, and 10% require TUR of the prostate, with subsequent risk of stress urinary incontinence. During the first few days the appearance of blood in the urine is common, and in the first few months, a burning sensation in the urethra and increased urinary frequency.

Sexual problemsErectile function progressively declines after brachytherapy, but compared to external radiation, only 25-40% of patients have severe erectile dysfunction at 5 years after completing treatment. In these cases, use of PDE-5 inhibitor medications is very helpful in restoring erectile function.

Radical prostatectomyRadical surgery, defined as complete resection of the prostate and seminal vesicles, is the best possible treatment for patients with localized (T1-T2) prostate cancer, since currently neither hormone therapy nor chemotherapy cure the disease, and not all the cancer cells can be eradicated using radiation therapy or other forms of energy. Radical prostatectomy is the only treatment that can ensure absolute cure in 95% of patients whose PSA levels have not changed over 10 years after the intervention. The main advantage to this treatment is that it offers the possibility of a cure without greatly affecting surrounding organs, and on the other hand, greatly improves obstructive urinary symptoms in those patients who also have obstructive BPH in addition to a malignant tumour. The factor that best determines success of the intervention, beyond technological considerations, is the experience and expertise of the surgeon.

Retropubic radical prostatectomyIt is performed under regional (intraspinal/peridural) or general anaesthesia. The urologist makes a vertical incision from the pubis to the navel. The space containing the bladder, prostate, and seminal vesicles is then entered without cutting any muscles. In some cases, if there is suspicion the cancer has reached lymph nodes, these will also be resected and analyzed. If prior to surgery the patient has normal erections and the tumour is confined to the prostate, it is important to preserve and avoid damaging the erector nerves that descend on both sides of the prostate in order to recover erectile function over several months. It is also very important to preserve the external urethral sphincter to maintain good urinary continence in more than 90% of patients. Once the prostate and seminal vesicles are resected, the bladder is joined with the urethra. The surgery lasts between 1.5 to 2 hours. A catheter is left in the bladder that is then removed 7-10 days after the intervention. The hospital stay varies between 5 and 7 days, and normal activity can be resumed 2-4 weeks after the intervention. A recent published study shows that 93% of patients undergoing radical retropubic prostatectomy are satisfied with the elected treatment. Currently, it is the surgical technique with the best long-term results, not only in controlling the cancer but also in conserving erectile function and urinary continence.

Perineal radical prostatectomyIn this case the incision is created in the perineum (between the anus and the base of the scrotum) and the prostate is reached from there. The length of the procedure is shorter and with less bleeding than in retropubic radical surgery, but it is more difficult to preserve the erector nerves.

Laparoscopic and robotic radical prostatectomyThis is performed under general anaesthesia. Instead of a single incision, 5 small incisions are made through which a camera and different surgical instruments are inserted. It can also be performed in a similar manner with the Da Vinci robot, with the only difference being that the surgeon manipulates the instruments through a robotic interface. The operating time is about 3 to 4 hours. The only advantage over open radical surgery is less blood loss (and therefore lower rate of needing transfusion) and a somewhat shorter hospital stay, about 3 to 4 days. This type of surgery is not recommended in patients with previous radiation treatment or who have undergone pelvic surgery. Long-term results are not yet available for laparoscopic techniques, and for the moment, available data do not demonstrate superiority of these techniques in terms of oncologic and functional efficacy (erectile function and urinary continence).

What are the risks of radical prostatectomy?

Urinary problemsThe most common problem is stress incontinence, that is, leaking of urine when coughing, sneezing, or lifting weight. With resection of the prostate, a portion of the continence mechanism (external urethral sphincter, intimately linked to the prostate) disappears, and what remains of the mechanism does not guarantee absolute continence in the beginning. However, about 90% of patients that have been operated on by very experienced surgeons do not suffer this urinary disorder.

Sexual problemsIf is not possible to preserve the erector nerves, there will be complete erectile dysfunction. When erector nerves are preserved, erection capacity may be progressively recovered. In the first few months after surgery it is not possible to have spontaneous erections, and pharmacological or other types of treatments are necessary to recover proper erectile function as soon as possible.

What can I expect during the post-operative period after a radical prostatectomy?After waking up from anaesthesia, you will notice you have a urinary catheter and a drain in the abdominal cavity. The catheter will remain in place for 7-10 days and the drain is usually removed after 2 days. Usually you will also receive IV fluids for about 24-48 hours until ingestion of liquid and solid foods is tolerated. At 7-10 days after the intervention, your urologist will remove the urinary catheter and will explain a series of exercises (Kegel exercises) to reinforce the urinary continence mechanism. During the first few weeks, some urine leak is normal when standing, coughing, or doing exercise, but this improves progressively; over a few months (3-6 months), 95% of patients under 50 years and 85% of patients over 70 years are continent.A few days after surgery, the specialist receives the report from the pathologist regarding the prostate, seminal vesicles, and in some cases, the lymph nodes resected from the surgery. If the cancer is localized (T1-T2), there will be periodic follow-up visits with measurements of PSA levels, which should be below 0.1 ng/ml. If the tumour is locally advanced (T3-T4), or has invaded lymph nodes (N1-N2), further treatment with external radiation and/or androgen block (hormone therapy) is recommended.

Can the ability to have an erection be recovered after radical prostatectomy?Yes, assuming the surgeon has been able to preserve the erector nerves. Recovery of erection capacity depends on the age of the patient and erectile function prior to surgical intervention. About 95% of men between 40 and 50 years attain an erection sufficient to allow coitus. This percentage decreases with age: 85% for patients 50-60 years, 75% for patients 60-70 years, and 50% for patients 70-80 years. It is imperative that at 6 weeks after the intervention drug therapy be initiated using PDE5 inhibitors (sildenafil, vardenafil, or tadalafil), prostaglandin E1 (intraurethral or intracavernous injections), or vacuum devices. If no response is obtained with these other treatments, placement of penile implants may be considered.

Is an ejaculation possible after radical prostatectomy?No, since complete resection of the seminal vesicles and the prostate involves disappearance of the ejaculatory apparatus. During the excitation phase there is emission of a transparent fluid, which is secreted from the bulbourethral glands, and during orgasm contraction of the perineal muscles is noted, and occasionally, leaking of a few drops of urine due to contraction and relaxation of the external urethral sphincter which can occur normally during an orgasm.

Can one father a child after a radical prostatectomy?It is not possible through natural methods since the surgical intervention severs the connections between the testicles and the urethra, but semen can be frozen prior to the intervention, and then artificial insemination techniques may be used to father a child.

CryotherapyCryotherapy is a technique used in the treatment of localized prostate cancer (T1-T3a). Using needles (cryoprobes), through which high-pressured helium is circulated, ice balls are formed within the prostate, reaching temperatures of -40oC to -50oC which are lethal to the cells. The procedure is performed under general or spinal anaesthesia. Using transrectal ultrasonography, the volume of the prostate is measured and needles are placed through the perineum that penetrate the prostate. Correct positioning is then confirmed by cystoscopy, and a catheter is left in place to prevent cooling of the urethra. Next a catheter is placed within the bladder (suprapubic cystostomy) to drain the urine. Usually two cycles of freezing and rewarming are performed. The duration of the intervention varies between 2 to 3 hours. After 24 hours, the patient is discharged home with a urinary catheter that is removed 2-3 weeks after the intervention. In the first few days a certain amount of scrotal swelling and a tingling sensation in the gland are common, that usually disappear after a few days. This technique is not recommended in patients who have previously undergone TUR of the prostate, or in patients presenting with severe obstructive urinary symptoms. Neither is it indicated for prostates larger than 50cc, in men with inflammatory bowel disease, nor in cases of previous pelviperineal surgery. It is not recommended in patients who wish to preserve sexual potency.

What are the risks of cryotherapy?

Urinary problemsSevere urinary incontinence is uncommon, varying between 1-8%. In patients previously treated with external radiotherapy or brachytherapy, incontinence may affect up to 10% of men. Stenosis of the prostatic urethra and urinary obstructive problems due to detachment of necrotic tissues occurs in 1-15% of patients.

Sexual problemsFreezing of the erector nerves carries an extremely high risk of complete erectile dysfunction, affecting about 93% of patients. Cryotherapy is therefore not recommended in patients who wish to maintain their sexual potency intact.

Intestinal problemsThe most serious complication, though rare with modern cryotherapy techniques, is the appearance of a communicating tract between the rectum and the urethra (rectourethral fistula) in about 0.5% of patients. This percentage of affected men increases up to 3% in patients with previous radiation therapy.

High-intensity focused ultrasoundThe HIFU technique is based on thermal destruction of the tissues. This new form of treatment was discovered in 1940 and its use in patients with prostate cancer began in 1995. The acoustic energy (ultrasound) emitted from a transducer placed in the rectum is absorbed by the prostatic tissue and is transformed into heat, reaching intraprostatic temperatures of 98-100oC that destroy the prostatic cells. Precise ecographic control avoids damage to surrounding tissues. This technique is recommended in patients with localized prostate cancer (T1-T2 N0 M0) who are not good candidates for radical prostatectomy or who do not opt for the surgery. It is not indicated in patients with prostates larger than 50cc, or in prostates with calcifications longer than 1 cm. Currently HIFU techniques are being developed using endorrectal magnetic resonance imaging instead of ultrasound images, which will optimize the treatment in the future.

The procedure is performed under general or spinal anaesthesia, lasting approximately 1 to 4 hours depending on the size of the prostate. The patient is discharged after 24 hours with a catheter in the bladder (cystostomy) that is then removed after 2-3 weeks.

What are the risks of HIFU?

Urinary problemsAbout 15% of patients experience urinary difficulties due to narrowing of the opening of the prostatic urethra. Urinary incontinence is mild and may affect about 6% of patients. Inflammation of the testicle and epididymis occurs in about 8% of cases.

Sexual problemsAbout 30% of patients experience a decrease in erectile function, which improves with pharmacologic treatment.

Intestinal problemsA rectourethral fistula is very rare, with an incidence of 0.2% of patients.

Hormone treatment of prostate cancerThe prostate depends on male sexual hormones or androgens for its physiologic function. Ninety-five percent of these hormones are produced in the testicles (testosterone and dihydrotestosterone), and the rest are produced in the adrenal glands (androstenedione and dihydroepiandosterone). Testosterone is the most potent androgen and its production is regulated by LH-RH (also known as GnRH), a hormone produced in the hypothalamus. LH-RH in turn stimulates the hypophysis to secrete the hormone LH, responsible for activating the production of testosterone in the testicles. Once in the prostatic cells, the androgens bind to androgen receptors, which control the growth and development of the prostatic tissue. The goal of hormone therapy is to abolish the production of testosterone.

Hormone therapy is used in advanced cases of prostate cancer (T3-T4 N0 M0), along with external radiation and in patients with metastasis. Unfortunately, not all cancerous cells respond to hormone therapy, therefore after a few years other treatment modalities may be necessary.

How is the treatment performed?There are four therapeutic options: orchiectomy, anti-androgens, LH-RH inhibitors, and estrogens.

What is orchiectomy?Orchiectomy involves resection of the testicles (castration). It is the simplest and most effective method to lower androgens in the body. The procedure is performed through a small incision in the scrotum and tends to be performed under regional or local anaesthesia, on an outpatient basis. After 24 hours, testosterone levels are reduced in 90%. The draw-back is that it is irreversible and carries psychological and cosmetic problems, which is why currently 75% of men prefer other pharmacological treatments. The main advantage of orchiectomy is that it has fewer adverse effects than the other treatments, and patients report better quality of life.

What are the anti-androgens?Anti-androgens are drugs that act by binding to the androgen receptor, preventing the androgens from interacting with prostatic tissue. There are two types of anti-androgens: steroidals, such as cyproterone acetate, and the non-steroidals, such as flutamide, bicalutamide, and nilutamide (the last not available in Spain). Currently, use of steroidals is not recommended due to severe cardiovascular complications seen in up to 10% of patients. The non-steroidals are used in combination with LH-RH inhibitors over 2-3 weeks. Among their most common adverse effects are gynecomastia and mastodynia (increase in the size and sensitivity of mammary glands), inhibition of sexual desire, erectile dysfunction, diarrhoea, hepatic toxicity (flutamide and nilutamide) and pulmonary fibrosis (nilutamide).

What are LH-RH inhibitors?This group is comprised of two types of drugs, the LH-RH agonists and the LH-RH antagonists. Their action is also known as chemical castration.

LH-RH AgonistsThese act at the level of the hypophysis, stimulating LH-RH receptors so that within a few weeks, LH hormone is no longer released and the testicles stop producing testosterone. The most widely used LH-RH agonists are triptorelin, goserelin, leuprorelin, and buserelin. They are administered by subcutaneous or intramuscular injections every 3 to 6 months, using sustained release delivery systems. Given that at initiation of treatment there is a notable increase in testosterone levels that lasts 10 to 20 days, concomitant administration of an anti-androgen is necessary.

LH-RH antagonistsThese act at the level of the hypophysis, blocking the LH-RH receptors in the hypophysis and rapidly lowering the concentration of LH and testosterone. The only drug in this category is Degarelix, approved by the FDA in 2008, but not yet commercialized in Spain. The main advantage of this drug is that it does not require the use of an anti-androgen.

What are the risks of hormone therapy?The majority of patients complain of fatigue, weakness and emotional disturbances. Hormone therapy is associated with a notable decrease in quality of life. The most common adverse effects include:

OsteoporosisOsteoporosis is loss of bone mass. After four years of hormone therapy, osteoporosis is very common among patients. Measures that can improve bone density include smoking cessation, physical exercise and vitamin D and calcium nutritional supplements. Bisphosphonates and estrogen patches also increase bone mass.

Hot flashesThese are described as a sudden sensation of heat in the thorax and face accompanied by sweating. These are very similar to what occurs in menopausal women. They affect from 50-80% of patients. Drugs such as megestrol acetate, venlafaxine, and estrogen patches are used to control hot flashes.

Sexual dysfunctionA reduction in sexual desire occurs in 95% of patients, and erectile dysfunction affects 80%. The latter can be palliated with the use of PDE5 inhibitors (sildenafil, tadalafil, or vardenafil), or with intracavernous injections of prostaglandin E1.

Cognitive disturbancesLoss of mental sharpness and anxiety disorders are common. Depression may be present in 13% of patients.

Loss of muscle massDecrease in muscle mass and weight gain are common, therefore maintaining an adequate exercise program is important.

GynecomastiaGynecomastia is associated with use of anti-androgens and estrogens. In order to prevent it, prophylactic radiotherapy treatments on breast tissue may be performed.

AnaemiaAnaemia may be caused by lack of testosterone, a key hormone in bone marrow for production of red blood cells.

Cardiovascular effects and diabetesThe risk of hypertension, myocardial infarction and diabetes is higher in patients undergoing treatment with LH-RH analogs.

Hormone therapy with estrogen patchesIn recent years, controlled clinical trials have shown the efficacy of estrogen patches as hormone therapy for prostate cancer.

What are estrogens?Estrogens are female sexual hormones that when administered in males, produce a reduction in LH and testosterone levels. In addition, estrogen has cytotoxic effects on tumour cells. In the middle of the last century, diethylstilbestrol, a synthetic estrogen, was already being used. However, it had to be removed due to high cardiovascular toxicity.Today, new forms of pharmaceuticals, such as estrogen patches used for menopausal women, allow for a good method of chemical castration in men, minimizing the cardiovascular adverse effects. There is currently a phase III clinical trial being performed in the United States, with preliminary results showing promise. The only adverse effects associated with the patches are sexual dysfunction, gynecomastia, and mastodynia.Treatment with estrogen patches not only avoids the adverse effects of current treatment options (osteoporosis, anaemia, hot flashes, diabetes, cognitive decline and cardiac problems), but also represents a savings of millions of Euros annually for our health care system.

Chemotherapy in prostate cancerChemotherapy is used for metastatic prostate cancer that has ceased responding to hormone therapy. Currently, treatment with docetaxel in combination with prednisone has been shown to improve symptoms and increase survival. Other drugs used include estramustine, mitoxantrone, doxorubicin, etoposide, carboplatin, and vinorelbine.

What are the risks of chemotherapy?Chemotherapeutic agents attack rapidly-dividing cells, thereby not only destroying the cancerous cells, but also affecting other body cells, such as those in the bone marrow, intestines, and hair follicles. The most common adverse effects include: fatigue, loss of appetite, nausea, vomiting, hair loss, and increased risk of infection.

New prostate cancer treatmentsImmunotherapy, directly applied through vaccines such as Sipuleucel-T (Provenge®) approved by the FDA in 2010, has demonstrated improved survival in hormone-resistant cancer cases. Other drugs under study include the angiogenesis inhibitors (thalidomide, bevacizumab), androgen receptor antagonists (MDV3100) and inhibitors of testosterone synthesis (abiraterone).